Steroid compounds



Patented Mar. 2, 1954 r ATENT OFFICE STEROID COMPOUNDS lli rankifl. rIiin-c oln,.Jr.,: and

1113.200, Mich, :assignors pany, Kalamazoo, Michigan George ligSperogKalato l ke Upjohn Gom- Mich, a corporation of NoDraWing. Application February26, 1952, -Serial No. 273,556

-18-Claims. .(Cl. 260-397A5) The: present invention-relates torcertain steroid compounds, and .is moreipartioularly concerned with :3;1 lu-,diacyloxy-r1'iehydroxyhregnane onesnmd .to a process. for the; production thereof.

.Thenovel compounds :of the .gpresentrinvention may-he represented by the formula:

wherein A100 is -an acyloxy group, he being the 'acyl'ra'dical of an organic carboxylic'acidg-especially such acids *containing from :one to eight carbon atoms, inclusive. "The configuration of the 3-hydroxy group 'in the above formula and elsewhere in this "application includes both aipha and beta forms unless "otherwise specified, "and theponfiguration 'of the 1.7 -hydrox-y1grcup in the above formula and elsewhere "in this application isal-pha.

"It is an object'o'f the present invention to provide 'a group 'of -novel compounds, Bile-diatomoxy-17hydroxypregnane=20 ones, which have utility in the preparation of biologically-active compounds, such 'asc'ortisone and its derivatives, and which are alsophysiologically active per se. A further object or the invention 'is the provision oTa process'forthe produc'tionof thenovel 3,1 1- diacyl'oxy l7-hydroxypregnane 20-ones. Other objects "ofthe invention will be apparent to 'those skilled 'in the art to which this invention per- Twins.

The compounds of the present invention, the 3,-1-1a diacyloxy l7 hydroxypregnane-20-ones,are useful derivatives of the starting -3,'-1la,"1'7-trihydroXypregnane ZO 'ones and l-lu-acyloxy alq- "dihydroxypregnane-20 ones, as 'well as mixtures of these starting "compounds, the compounds of the present invention being much easier to sepa rate, isolate, crystailize, purify, and itlentifythen the "starting compounds, especially the 3,1laI-I7- trihydro-Xypregnane-ZG=ones. The compounds of thisinvention-also are easier to 'han'dle, stora-and transport than the startin'g com-pounds since they aremore stable to deterioration by light, moisture, and other factors normally encountered in "handling, storing, 'and transporting chemical compounds. The :"compounds :of :the

,2 present invention, the 3,11a-diacyloxy-l;'l-hydroxypregnane-20-onea and the starting scorn- ;pounds;the 3,1.1owlT-tIihE GITOXYpIQgnaHS-2O-OI1ES and the ll a-acyloxy-aii,l7-dihydroxypregnane 20-ones,=-are.-useful in the preparation of other steroid compounds having an @oxygen atom at carbon :atom eleven, such as-cortisone acetate, which i may be: obtained from these compounds by known methods, for example, by hydrolysis of the three and eleven-acyloxy groups, if present, to three and eleven-hydroxy-groups losing acid or base, bromination with bromine inchloroform to-introducea bromine-atom-atthe 21 position, oxidation of the three and eleven-hydroxyl groups .to ketone groups Vusingchromicfioxide, replacement of the 21-bromine by a ZJ-acetoxy group using potassium acetate :in acetic acid, bromination withbromine :in acetic acidtodntroduce-a \bromineiatom at the tounpositiom-treatment :with semicarbazide to introduce a double bond attthe dour-position loyremoval of hydrogen bromide, the semicarbazone of the threehetone group also being :formed in this step, and Lhy- .drolysis v of the semicarbazone with pyruvic acid to regenerate theuthree-ketone. .Suchcomp ounds are of i-particular interestuin theufield of steroid research due to the biological activitygof the cortical hormones and certain known derivatives thereof. .The importance of .suchlinvestigationuis moreovervemphasized .by'the shortage .of adrenal cortical hormoneaand the absence .of any present suggestionifor the alleviationof said short- .age except through organic synthesis.

The 3;llaediacyloxy-I'LhydrOXypregnanesZ'O- ones which are of particular interest are those compounds of .theabove generic formula wherein AcO represents an .ester of the three and eleven .hydroxyl groups with an organic rcarboxylic acid containing up to and including eight carbon atoms. Among suchiacidsarerformic, acetic, pro- .pionic, butyrio, valeric, hexanoic, heptanoic, cctanoic, cyclopentanecarboxylic, cyclopentylpropioniqbenzoic, toluic, and lthelike. Preferred are those ester groups derived from the loweraliphatic acids, especiallyrthose containing from one to eight carbon atoms, inclusive. The acids may also contain substituents, such as halo, alkyi, and 'methoxy, which are non-reactive under the reaction conditions employed. 'Thethree and eleven-acyloxy-groupsmaybe the same, or different, dependingon the starting cunspoilt-ids.

According to the novel process or the present invention, SJ Iu-di'acylOXy-lWhydroxypregnam- 20-ones :Uf ithe shove :generic :formulaare carepared by Iest'erifi'cation of :thewthreeand elevenhydroxy groups vin-a starting 3,11u,'1'7-trihydroxypregnane-ZO-one, or by esterification of the three-hydroxy group in a starting lla-acyloxy- 3,l'l-dihydroxypregnane-ZO-one, or by esterification, as above, of a mixture of an lla-acyloxy- 3,l7-dihydroxypregnane-ZO-one and a corresponding 3,11a,17 -trihydroxypregnane-2O one. The esterification is accomplished by using an acylating agent, especially those providing an acyloxy group containing from one to eight carbon atoms, inclusive, with or without the addition of a solvent or catalyst.

In carrying out the process of the present invention the starting compoun or mixture of starting compounds, as described above, is admixed with an acylating agent. Preferred acylating agents are the acid halides, preferably the acid chlorides, and the acid anhydrides derived from organic carboxylic acids containing from one to eight carbon atoms, inclusive. Among such acids are formic, acetic, propionic, butyric, valeric, hexanoic, heptanoic, octanoic, cyclopentanecarboxylic, cyclopentylpropionic, benzoic, toluic, oxalic, and the like. The acids may also contain substituents, such as halogen, alkyl, methoxy, active under the reaction conditions employed. Usually free formic acid, rather than the acid anhydride or acid halide, is used to prepare the formate esters. The amount of acylating agent used is usually at least the theoretical amount.

However up to fifty or sixty times the theoretical amount, or even more, may be used, with from two to ten times the theoretical amount usually being preferred. Frequently it is preferred to use an esterification catalyst such as pyridine, a picoline, a. lutedine, a collidine, or other basic compound, with pyridine being preferred. The resulting mixture is then allowed to stand, with or without stirring, at a temperature between about zero and about 100 degrees centigrade, with room temperature being entirely satisfactory in most instances, for a period of time between about one and about 24 hours, or even longer, the precise reaction period depending in part on the starting compound, the acylating agent, the temperature, and the esterification catalyst, if one is used, with a reaction period of from about eight to about sixteen hours being entirely satisfactory in most instances. The 3,11a. diacyloxy ones may be isolated from the reaction product in any convenient manner, for example, by pouring the reaction product into water, allowing the resulting mixture to stand for a period of time to permit decomposition of the excess acylating agent, usually two to four hours being sufiicient, collecting the precipitated solid, washing the solid with water, and drying the resulting solid under vacuum. If desired the product may be further purified by conventional procedure, such as recrystallization from an organic solvent which is non-reactive with the 3,l1a-diacyloxy- 17-hydroxypregnane-20-one obtained. It is sometimes preferred not to dry and recrystallize the product, as the wet solid, after being washed with water, is frequently of sufficient purity to be suitable for use in subsequent reactions.

The starting compounds for the method of the present invention are 3,1la,l'T-trihydroxypregnane-20-ones and 11e-acyloxy-3,i7-dihydroxypregnane-20-ones wherein the eleven-acyloxy group is an ester of the lla-hYdIOXY group with an organic carboxylic acid containing up to and including eight carbon atoms. Among such acids are formic, acetic, propionic,

and others, which are non-re- 1"! hydroxypregnane 20 butyric,

valeric, hexanoic, heptanoic, octanoic, cyclopentanepropionic, cyclopentylpropionic, benzoic, toluic, and the like. Preferred are those ester groups containing from one to eight carbon atoms, inclusive. The acids may also contain substituents, such as halogen, alkyl, and methoxy, which are non-reactive under the reaction conditions employed. The eleven-acyloxy group of a starting 1la-acyloxy-3,17-dihydroxypregnane-20-one is unchanged from the eleven-acyloxy group present in its precursor. The starting 3,1la,l7,-trihydroxypregnane-20-ones and llaacyloxy-3,1'T-dihydroxypregnane-2ll-ones, or mixtures of a 3,11 l!-trihydroxypregnane-20-one with a corresponding 11u-acyloxy-3,l7-dihy droxypregnane-ZO-one, are prepared from 1'7- (20) -oxid0-3,l1a,20-triacyloxypregnanes by a reaction in which 17(20)-oxido-3,1la,20triacylpregnanes are treated with a saponifying agent. The 17(20) -0XidO-3,11a,20- triacyloxypregnane is dissolved in an organic solvent which is substantially non-reactive under the conditions of the reaction, such as methanol, ethanol, acetone, or dioxane, with ethanol being preferred. The resulting solution is then admixed with an aqueous solution of a saponifying agent, such as sodium .hydroxide, sodium carbonate, or other basic saponifying agent,with sodium hydroxide being preferred. Use of an excess of the saponifying agent required completely to hydrolyze the 17(20) -oxido-3,1la,20-triacyloxypregnane, four to twenty gram equivalent weights, or even less or more, of the saponifying agent to one mole of the starting material, the preferred ratio being about ten to one, yields 3,l1a,1'I-trihydroxy pregnane-20-one. Use of the exact amount, or even less, of the saponifying agent required completely to hydrolyze the 17(20) -0XldO-3,11a20- triacyloxypregnane gives products from which both a 3,11a,17-trihydroxypregnane-20-one and an 11a-acyloxy-3,17-dihydroxypregnane-20-one may be isolated. The resulting mixture is then permitted to stand for about fifteen minutes to about two hours, or even longer, the exact time depending in part upon the temperature, in part upon the 17(20)-oxido-3,11a,20-triacyloxypregnane employed, and in part upon whether complete or partial hydrolysis is desired. A longer time is generally preferred if complete hydrolysis is desired, and a shorter time is generally preferred if incomplete hydrolysis is desired. Temperatures between about zero and about 100 degrees, or even lower or higher, may be employed, room temperature being entirely satisfactory in most instances. In general a. higher temperature gives a more rapid and more complete hydrolysis, and a lower temperature gives a slower and less complete hydrolysis. After completion of the desired reaction, the product may be isolated in any convenient manner, such as, for example, extraction with an organic solvent, such as chloroform, washing the extract with various solutions, such as aqueous sodium chloride and water, drying the washed extract with a drying agent, such as anhydrous sodium sulfate, removing the drying agent by filtration, and evaporating the organic solvent. The residue obtained after removal of the solvent may be purified and separated into components, if hydrolysis has been incomplete, by conventional procedure, such as chromatographic adsorption, fractional crystallization, and the like. Sometimes, it is preferred not to purify the product since the residue obtained washed and dried extraction solvent is of suitafter removal of the hexenoie, he tenoie; 'oetamei'e, eyelopenten'ecaz teeync, eyeioperit'yHt-ropionic," temei mum, and:

the like; Preferred are those esterg'fdu ts derived fiom; the lowei -aflipha "0 2.0165; espeeie lly'tliose eent'aining from one wei h-t eerbmetemem elusive. The acids a-lsooonteifisubstituents; su'cfies halo; eIky-I, etIidrietfiGKM-Whicfi ere nen reactive under the reaction conditions employed The three, eleven, -a-22dtwenty-ester groups may be the same, or two ester groups may be the same be different, depending on tfie prebu-rsorsy'sihoe tHe ester groups of the 17"("2'0')-oX1'do-*3,II;20-- macylexyeregnanesai'e' unchanged from those in the: precursors: The 17 (20)'--oxido=3;11%z, 2o= triecylbxypregnanes" are prepared by an oxide tion reaction in which an" atom of oxygen is adfied to the 17(20) -ethy'1enib" 'Iihka'ge iz'r a 3,111g20 trieeyIoxy-1"7" '20=pregnene. Any oxfdint or" epoxi'd izing" agent capable offurnishihg the necessary oxygen may be employed. The agents most commonly used are hydrogen peroxide and organicpera'cids, for 'exelnpfe'; peraeeti'e; erpro' ibni'c; perbuwric; perbenzoie; or cfiioropefztc'eti'c. The reaction is carried out. by mixing together the 3,1Iu;2i')-triacy1bXy-.1T(20')'- pregnene and the pera'c'id of'choice; preferably peracetio aczd or hydrogen peroxide, for a suitable .per1od,.e. g., from about one-half to. twentyfour hours; the le'z'lgth of time depending upon the ceneemrzttibn of oXygen-fufniShing ag 'ent'. When the" oxidaz ltis hydi ogen peroxide. gllaci'ai alc'et'ic' acid" is a, convenient reaction medium. When a; pera'cidi s' emp'1dyed',.any off the customeryergenib s'olvezits i'n the startihgrsteroid. is soluble can be used, such as. c1'11oeof01tm, .carbon tetracl'lioride, ethylene dich1oride,.methy1-- en'e' chloride, mixtures of. ether and. chlorofonm afid' Others, with cnlovo1-fc'arm. beiiflg.preferrei- It 1' sometimes desirable to slzili t'o the oxidizing medium a, smali quantity of an alkali metal-sal-t residue from any orga-nicsolvent. Whichis! nonreactive with the oxide. It is sometimes prefel red not to crystallize theprod-unt, as: the" res idueobtatned after removal of the-solvent is: of suficien-t purity to be used: in subsequentre aetiens;

The 3=,1 lw,2G-triacy16Xw--1 7 2 0") -pregnenes1 used toprepare 1 ?(Mfr-oxide-3;Im2!)-ti*iicylozty pl egnanes' cam be produced by various proceduress Ehe 3a,1.1w;2o=trieoy1oxy-I 'HEW-pfig nenes are conveniently plfepa-red heating 3w,na -dihydroxypregnantezil oneg a. 1 Iu--acyI-- ox e3a hydroxypregnane fi0 one; ora'. 3d', I -Ia-df-' acylozqwpregnenezmorse; each prepared from progesterone as d-esex ibedl below; a; large excess; of; an: weenie canbexyl-ic eeia eml-izyzei icre ativel.

6 m me px'esence 0'15 a' *aeid eeiiatyet seem sur mil-ic ecfit Sui-ionic e d er-id the-like; nam teiuefiesulfome acre being referred; The terefs heatedusuefl y e 5 elven-t 10o te 180 'de-' greee. eentieraee; preferet l a ttheboi i-i n pomt, anti-1* the ennydnideie nearly com letel yremevecr by =c1is'tii1ati6ng require a} period or about hours. The rate of distm'etien: may be faster er's-Iewee, 33nd any' peri od of etout two" hours-to eight hours or: even shorter o f-lbn 'en' is; deemti ve It tfie en nydwide used" has he efiltt o r is a solid azsu it able soLW'e'rYt such temefie, xylene-,paireffi n hy'eirobafb'ons; or the -mey be used to 'e'ontro1' the tempeeetu -l e1 re"d anl 11yd1"ide is aeetieenfiydeid at? am pen yd l i'eies. such eeprepionic, butyfie 'vel ez i'e, "o'i'e; flee-tenets; and ostenoioanhyd ni'des; aiS W'eII- als benzoic acid inn-hydride, orthotel-me e'nhydriee, aid tll'elii ie a l -e' azl'soopeeanl iy rides can aIso' be substi teted withnon reaot' .e gro'L'ms, such as new. at and metho xy, as in the ease of chlore'ac'e ortho toluie; or' metfi'o'xybenzoio atofd why-- dvidesi Undlez" the conditions of the reaction, hydmxyrgrommet-carbon atomsthreeand-eleven M11 lee-ac E'atedi The See-L1wdihytfiox ypregnahe-"D -one, the 3 1a,;e diaeyloxmeregnehe 2O-o1es, and the Haw gilan'e -on'esare pre- 1 progest He by the foHewih reactions Pregsterone is 0'xid- "*ed t0- l la-hydroxy pl egesterex'ie by a; fermente onprocess more m y desk I- ed fr; P'i'epera'tion 1. Tire lla hy' di 'fi-ypFo'gest'e'rone redeced with hydrogen in; thefioil e'sm e, palfied ifim cl-iarcoal catalyst to lla hydroxyor'egnene=82fl diohe. REdUC ti'oxf o1 tbgeflwhydro; gnene-332o-dibne with soei'um borohydi .negfi/"esthe"o'tesire'd' 1 Que-20 0119.

Le, to give an llu acyloxye, followed by reduction of" 1'fia faydrexypregoene sZ20 dione with en um 'bbiohydri'de in dioX-ene', gives the desired be prepea m from l le ecyloxy 3y3 hycirorypreg fiene -w ones in the s manner as described diones, prezfere'd'from progesteyone esdescribe'd I process Mid-products of the present invention}.

about 55.5 and about-519i Te fool liters of the medium-centeihm a: 32" to 48 hour grewfli; at" robm-temeereture with aeretien; of Rm'eome arrhizus, was added one gram of progesterone in fifty milliliters of acetone. The culture was then incubated at room temperature for 48 hours. At the end of this time the pH of the medium was 3.5 and the fermentation liquor and mycelia were extracted successively with three one-liter portions, one two-liter portion, and one oneliter portion of methylene chloride. The methylene chloride extracts were combined and washed with two 400-milliliter portions of two per cent aqueous sodium bicarbonate solution and three SOD-milliliter portions of water. The methylene chloride extract was evaporated to dryness in vacuo and the solids taken up in fifty milliliters of methylene chloride. The solution was transferred to a 100-milliliter beaker and evaporated by a stream of air. The solids, weighing 1.585 grams, were dissolved in five milliliters of hot methanol and allowed to cool slowly at room temperature, whereupon 75 milligrams of crystals separated out. The mother liquor was freed of solvent by aeration, dissolved in fifty milliliters of benzene, and chromatographed over alumina (A1203). Fifty grams of acid-washed alumina, dried at 45 degrees centigrade, was used as adsorbent and 100-milliliter portions of solvents were used to develop the column. The solvents and the order used were as follows: benzene, benzene, benzene plus per cent ether, benzene plus 5 per cent ether, benzene plus 10 per cent ether, benzene plus 10 per cent ether, benzene plus 10 per cent ether, benzene plus 50 per cent ether, benzene plus 50 per cent ether, ether, ether, ether plus 5 per cent chloroform, ether plus 5 per cent chloroform, ether plus 10 per cent chloroform, ether plus 10 per cent chloroform, ether plus 50 per cent chloroform, ether plus 50 per cent chloroform, chloroform, chloroform, chloroform plus 5 per cent acetone, chloroform plus 5 per cent acetone, chloroform plus 10 per cent acetone, chloroform plus 10 per cent acetone, chloroform plus 50 per cent acetone, chloroform plus 50 per cent acetone, acetone, acetone, acetone plus 5 per cent methanol, acetone plus 5 per cent methanol, acetone plus 10 per cent methanol, acetone plus 10 per cent methanol, acetone plus 50 per cent methanol, acetone plus 50 per cent methanol. The chloroform and chloroform plus five per cent acetone eluates were combined, evaporated to dryness, and the residue dissolved in two milliliters of hot methanol and filtered. After overnight refrigeration, 171 milligrams of crystalline lla-hydroxyprogesterone, melting at 166 to 167 degrees centigrade, was obtained. A sample recrystallized from methanol gave the following constants: melting point, 166-167 degrees centigrade; fal plus 175.9 degrees (chloroform).

AnaZysis.-Per cent calculated for Carl-130032 C, 76.4; H, 9.10. Found: C, 76.6; H, 8.92.

The structure of this product was further established by its conversion, with chromic acid in acetic acid, to 11-keto-progesterone [Reichstein, Helv. Chim. Acta, 23, 684 (1940); ibid. 26, 721 (1943)].

PREPARATION 2.11wHYDRoxYrREcNAnn-3,2O-DI0NE grams of a thirty per cent palladium-charcoal catalyst in a Parr apparatus with an auxiliary mercury manometer. The time required for the hydrogenation was about twenty minutes. The reaction mixture was filtered and the solvent was evaporated to yield 265 milligrams of material melting at 145-185 degrees centigrade. This product was extracted with a mixture of one milliliter of ether and nine milliliters of Skelly Solve B. On standing, the extract deposited eighty milligrams (32 per cent) of lla-hydroxypregnane-3,20-dione as feathery needles which melted at 85-90 degrees centigrade. Recrystallization from a mixture of about six drops of ethyl acetate and five mlliliters of Skelly Solve B did not change the melting point.

Analysis-Per cent calculated for C21H32O31 C, 75.86; H, 9.70. Found: C, 76.13; H, 9.63.

Pncmmrron 3.-3a,11n.-DIHYDROXYPBEGNANE-QO-ONE To a solution of 5.31 grams of lla-hydroxypregnane-3,20-dione of Preparation 2 in milliliters of peroxide-free dioxane maintained at fifty degrees centigrade in a water bath was added a solution of 195.5 milligrams of sodium borohydride (assay 84 per cent) in five milliliters of water. The mixture was stirred for one hour at fifty degrees centigrade, filtered, acidified with three normal aqueous hydrochloric acid solution, and evaporated under reduced pressure. The residue was crystallized from fifty milliliters of ethyl acetate to give 1.95 grams (36 per cent) of 3a,11o. dihydroxypregnane 20 one, which melted at -182 degrees centigrade. An additional 0.2 gram melting at 181-183 degrees centigrade was obtained from the filtrate; total yield, 2.15 grams (40 per cent).

PREPARATION 4.11a-AoirroxYrREeNANE-3,20-oronn PREPARATION 5.--11a-acnroxyfia-rrynnoxrrancNANE- ZO-ONE To a solution of 200 milligrams (0.534 millimole) of 11a-acetoxypregnane-3,20-dione from Preparation 4 dissolved in ten milliliters of peroxide-free dioxane at fifty degrees centigrade was added dropwise with stirring a solution of 6.9 milligrams (0.152 millimole based on pure reagent) of sodium borohydride (assay 83.5 per cent) in one milliliter of water. The mixture was stirred at fifty degrees centigrade for one hour and acidified by pouring into fifty milliliters of water containing hydrochloric acid. The oil which first separated crystallized on standing. The solid was collected, washed with water, and dried under reduced pressure at fifty degrees centigrade. The yield of 11a-acet0xy-3a-hydroxypregnane-ZO-one melting at 122-136 degrees centigrade was 156 milligrams. The crude product was dissolved in fifteen milliliters of benzene and chromatographed over 7.5 grams of acidwashed alumina which had been dried at 120 degrees zcentigra-cle. The -.column"-.was :deneloped with-two fifteen :milliliter portions ;ofieach cf the following seventeen :solvents: benzene, benzene andw5, 10, and ;50:per cent ether, -ether,.etherxand 5, I0, and :50 per cent chloroform, chloroform, chloroform and i5, .110, and ;50 per cent acetone, acetoneand 5, 510, and 50 .per .centzmethanoLzand methanol. The product appearediin afra'ctions 1'2 (ether and 5 per cent chloroform) through .322 tchloroform and pericent acetone). Combination of these fractions and recrystallization from ethylacetate-Skelly-Solve gave 93.:milligrams of: product melting at 140-143 :degrees centigrade. Two further. recrystalliza'tions from isopropyl ether gave pure 'lla-acetoxy-fia-hydroxypregnane--one, melting at 146-4148 degrees cen'tigrade.

.Analysi's.-Pe1' 'cent calculated for iC2sHa641 0, 73.4; H, 9164. Found TC, 73:8; H,9.'61.

'BREPARATION iGw3a,l1a=DIACETOXYBBEGNANEQO-ONE "Usingthe procedure.described.:imBreparation-a, the v11a acetoxy ;3a-- ydroxypregnane 20-one from Preparation 5 was esterified with acetic 8.11" hydride in pyridine to yield 3a,11a-,diacetox;ypregnane-120eone.

PREPARATION '7.3a,11a;2-0 T1iIAoEToxY-17"( 20) PREGNENE Using the same procedure as .in .-;Breparation '17, 51.0 :gram .oi 311,1ladiacetoxypregnane-zoeme .frnm'IPreparation36'wasftreatedwithl0z45 gram of =para-ztoluenesulfonic :acid and Y100 milliliters 50f 'aceticanhydride. The yield of ;3a;1'1a;20-;triacetoxy-17 t20)-pregnene was 0.7 gram, melting at 200-210 degrees :centigrade. A :sample arecrystallized for analysis from acetone hexaneiand from aloohol'melted at 211-213 :degrees -:centi grade b1 minus 16 :degrees (chloroform) Analysis-Per cent calculated fOI' C27H400s: C, 70.4; H,-8.75. Found: C, 70.5; H, 8. 79.

PREPARATION 9.3a;11a,20-TRIAcEToxY-1'7( 20) .PREGNENE lUsing ithesame procedure .as :in Preparation 7, .2: 2 grams of Ila-.acetoxy-Ba-hydroxypregnane- 20-:one from Preparation :5 was 'treated'with .1206 grams 'of para-itoluenesulfonic acid and 240 milliliters of aceticanhydride. 'The' yield'of 3a;1'1a;20- triacetoxy 17(20) -pregnene, melting 'at :203208 "degrees centigrade, was 1 154 grams.

PREPARATION 10.3a,11a,20-TR11 ROPIoNoxY-17 20) PREGNENE Using the procedure described in :Preparation ,7, .Be lineclihydroxypregnaneafleone 'from .Prep- .arationia isrconverted to 3a,-11a,20-tripropionoxy- 17-12 0) emegnen-e rwithzpropionic ranh-ydride :in the presence cf-naraetoluenesulionic acid. PREPARATION fll.3a,11womomoxxQfil-rnorrowoxx- 17620) =P'REGNENE Using the procedure described ,in Preparation .8, .3 11111.ediacetoxypregnaneem-one from .Preparation :6 is converted to .3aAJm-diaCetOXy-2D-QI pionoxy-lf? (20) -pregnene with propionic anhydride in'thepresence ofpara-toluenesulfon'ic acid.

PPEPARATION 12.3fl,11a,20-TRIAOIFIOXY:17 (20)- reaeucmr .Using the procedure described in Preparationg,

3e-hydroxy-lyia-acetoxypregnane --20.- one .Qpre- Dared by the reduction of the illwacetox-yprege nane-3,20-dione of Preparation 4 with hydrogen at .tWo to threeatmospherespressure in methanol at room temperature using "a Raney nickel catalyst), is converted'to 3B,11a,2'0-triacetoxy-17 (20) .pregnene with acetic :anhydridein the presence of:paraetoluenesulfoniczacid.

In. :the same manneras :given above,- iother .181: :(or B).,'1:1 ;20-:triacy1oxy 151-20) apregmnesme prepared, including ;3';9,=11a;20--ttripropionoxy- 17 (20)-pregnene; 3,3,1111. diacetoxy-201propionoxy-17(20)-pregnene 3a,2 0 -.dipr opionoxy 11aacetoxy-17 (20)-pregnene; 3 8,11a,20 trioctanoylwry- 1 1620) -pregnene 3a,20-di0ctanoyloxy-- l-lcpropionoxy-EI'I- (20)--pregnene; 3abenzoyloxy-11aacetoxy-20-butyroyloxy lfl'l20) pregnene; "Sad-'11:- diacetoxy- 20-- benzoylo -l' 7'( 20-) pregnene; 3a,- Ll-Q20 tributyroyloxy-IW20-)-pregnene; Build-a,- ZO-trivaleroyloxy-l'] (2.0) pregnene; 3q,l-1q,'2,0-t1i hexanoyloxy-l'I-l-ZO) pregnene; 3a,11a,20 triheptan oyloxy-1'7(20)-pregnene; and 3a,11a,20-t1',i00- tanuy'ioxy-l'l-(ZO) -jpregnene.

PREPARATION 13. 17.(. 2Q) -0xm o+v3a,11w,20- mBmcE'roxYeREsN-ANE One and one-half grams of 3a;1'1a,20-triace'toxy-17 20-)- pregnene from 'Preparation '1, 8 or-9-) was-dissolved-in*755 milliliters of chlorocooled in an ice bath to about five degrees centigrade. Three and three-tenths :milliliters of commercial *grade forty per cent paracetic acid solution in which -milligrams of sodium acetate had been dissolved was added, andthe resulting mixture was then shaken on a mechaniel shaking machine for "about two hours at :room temperature to complete the :reaction. The mixture containing the crude-product-was diluted-with-fifty -milliliters of methylene chloride and then washed with several'25 mil1i1iter portions of -ice-cold=five per cent aqueous sodium hydroxide solution followed by 25 'milliliter portions of water until the wash solution was neutralto pHtest paper. The neutral solution-wasdriedwith anhydrous sodium sulfate and then -"filtered "to *remove the drying agent. I he whitetcrystalline residue -.ob.tained on evaporating -.the :solventirom the clear, fligyfsolution melted at 210-213 degrees centigradegRB- crystallization'from a mixture of ethyl acetate and"SkellyiSolve 13 gave fiuify needles of 17(20) 'oxid0-*3a;1:1a,20triacetoxypregnane, melting at 214 217 "degrees -centigrade.

AnaZysis.-Per =cent "calculated for CzvH4bO1: C, "68:04; -H, 8.46. Found: =0, 08.33; 862, 0, 67590; H, 0238. g 1

PREPARATION .14.-17 (2Q) -'oxIDo-3a,11q.,20

TRIACETOXYPREGNANE 0ne=gramrof 3 ,=-1=1- ,20-.triacetoxy-.1 7 20 )-,-:pregnene ifrom Preparation 7, 8iort9) .was dissolved in fifteen milliliters .of .benzene .and .five @milli- PREPARATION 15-17 (20) -OXIDO-3a,lla,20 TRIPROPIONOXYPREGNANE Using the procedure described in Preparation 13, 3a,11a,20 tripropionoxy 17(20) pregnene from Preparation 10 is converted to 1'1 (20)- oxido-3a,l1(1,20-tripropionoxypregnane by oxidation with peracetic acid in the presence of sodium acetate.

PREPARATION 1G.3a,11a-DIACETOXY-l7 (20 -oxino-20- PBOPIONOXYPREGNANE Using the procedure described in Preparation 14, 3a,1la-diacetoxy-ZO-propionoxy-l7 (20) -pregnone from Preparation 11 is converted to 341,110.- diacetoxy 17(20) -oxide-20-propionoxypregnane by oxidation with perbenzoic acid.

PREPARATION 17 .-17 (20 -oXIn-3fl,11a,20- ramoaroxrrsnsnnnn Using the procedure described in Preparation 13, 35,111,20 -triacetoxy-l7(20)-pregnene from Preparation 12 is converted to 17(20) -oxido- 313,11a,20-triacetoxypregnane by oxidation with peracetic acid in the presence of sodium acetate.

PREPARATION 18.17 (20) -0XIDO-3{3,11d,20- TBIACETOXYPREGNANE Using the procedure described in Preparation 14, 35,l1a,20-triacetoxy-l7(20)-pregnene from Preparation 12 is converted to l'7(20)-oxido- 3,8,l1a,20-triacetoxypregnane by oxidation with perbenzoic acid. 7 V

In the same manner as given above in Preparation 13 through Preparation 18, other 1*? (20) oxido-3a (or 5),11a,20-triacyloxypregnanes are prepared from the corresponding 3a (or 13),- 11a,20 triacyloxy 17(20) -pregnenes, including 17 (20) oxido -3,6,11a.,2Q-tripropionoxypregnane; 313,11 diacetoxy 17(20) -oxido-20-propionoxypregnane; 11a. acetoxy 3a,20 dipropionoxy- 17(20) oxidopregnane; l7(20)-0Xid03fi,11a,20- trioctanoyloxypregnane; 3a,20 dioctanoyloxy- 17(20) -oxido-lla-propionoxypregnane; lie-acetoxy -3a-benzoyloxy-20-butyryloxy-17(20) -oxidopregnane; 20 benzoyloxy 3a,].1a. diacetoxy- 17(20) oxidopregnane; 17(20)0Xld0-3a,11a,20- tributyryloxypregnane; 17 (20) -oxido-3a,llu.,20- trivaleryloxypregnane; 17(20) OXid0-3a,11a,20- trihexanoyloxypregnane; 17 (20) -0Xld03a,11a,20 triheptanoyloxypregnane; 1'7 (20) -OXldO-3a,l1a,- 20-trioxtanoyloxypregnane, and the like.

PREPARATION 19.11a-Acn'roxY-3a,17-I 1HYni:oxYrnEc- NANE-20-0Nn AND 3a,11a,17-TRIHYDROXYPBEGNANE- 2.0-0NE Nine hundred milligrams 311,11a,20-triacetoxypregnane (from Preparation 13 or 14) was dissolved in fifty milliliters of alcohol, and to the resulting solution was added with swirling 113- milliliters of a 0.5 normal aqueous sodium hydroxide solution. After standing at room temperature for thirty minutesi the solution was extracted with chloroform, and the chloroform extract was then washed with twenty per cent aqueous sodium chloride soluof 17(20) -oxidotion and dried with anhydrous sodium sulfate. 75

l9, an alcohol solution of 17(20) The'drying agent was removed by filtration, and

the solvent was removed by evaporation under reduced pressure giving the product as a colorless, viscous oil. The oil was dissolved in 100 milliliters of benzene, and the solution was passed through a chromatographic column packed with ninety grams of Florisil synthetic magnesium silicate to adsorb the product. The product was eluted from the column by washing with the following solvent mixtures in succession: ten 100-milliliter portions of 5 per cent acetone and 95 per cent Skelly Solve B, ten l00-milliliter portions of 10 per cent acetone and per cent Skelly Solve B, and ten IOU-milliliter portions of 20 per cent acetone and 30 per cent Skelly Solve B. On evaporation of the solvents from the various fractions the product had been separated into two parts, both colorless, viscous oils. The product from the first fractions was lla-acetoxy- 3a,l'l-dihydroxypregnane-ZO-one, as confirmed by analytical data, and the product from the later fractions was 3a,11a,l7-trihydroxypregnane-20-one, identical with the 3a,11a,17tllhydroxypregnane-ZO-one obtained in preparation 20. The ratio was about one part of the acetoxy compound for every nine parts of the trihydroxy compound.

Analysis of 11a-acetoxy-hlfldihyclroxy-20- one.--Per cent calculated for C23H3605. C, 70.37; H, 9.25. Found: C, 70.30; H, 9.30.

PREPARATION 2O.--3a,11,17-TRIHYDR0XYPBEGNANE- 20 cm;

Six hundred and twenty milligrams or 17 (20) oxido 3a,11a,20 triacetoxypregnane (from Preparation 13 or 14) was dissolved in 55 milliliters of alcohol, and to the resulting solution was added in several portions with swirling 55 milliliters of a 0.5 normal aqueous sodium hydroxide solution. After standing at room tern.- perature for fifty minutes, the solution was extracted with chloroform, and the chloroform extract washed with twenty per cent aqueous sodium chloride solution and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by evaporation under reduced pressure to give 490 milligrams of product as an oil. The oil was dissolved in ethyl acetate and Skelly Solve B was added. After standing for several hours the crystals which had formed were separated and recrystallized from an acetone-Skelly Solve B mixture to give 340 milligrams of 3a,11a,17-tlihydroxypregnane 20 one; melting point, 184-486 degrees centigrade; [0.1 plus 52 degrees in acetone.

Analysis: Per cent calculated for C21H34O4.- (3,7196; H, 9.78. Found: C, 12.21; H, 9.53; C, 72.25; H, 9.66.

PREPARATION 21.3a,110.,17-TRIHYDROXYPREGNANE- 20-0NE PREPARATION 22.-3a,1"' n1nrnaoxy-lla-rizorionoxr- PBEGNANE-ZOONE AND 3a,].1d,17-TRIHYDROXYPREG- NANE-ZO-ONE Using the procedure described in Preparation i113 tripropionoxypregnane .flbm :Preparation was converted by treatment "with saniaqueous :sodium hydroxide solution to an oily product which .was separated into 3a;17-,dihydroxy-IhepropionoxypregnaneeZO-one and 311,11a,l7strihydroxypregnane--one. The ratio was about one part :of the propionoxy compound for .every seven parts of the trihydroxy icompound.

PREPARATION v23.11a.-AC132TOXYr3/3,17-DIEI;YDROXYTPREG- NANE-ZO-ONE AND 3,8,11a,17-TRIHYDROXYPREGNANE- 20cm PREPARATION '24.3fl,11a,17-TBIHYDROXYPREGNANE- Using the procedure described in Preparation 20, an alcohol solution of 17(20.)-0Xld0-3fl,11q.,20- .triacetoxypregnane (from Preparation 17 .or 18) was converted to 33,11 ,1'7-trihydroxypregnane- .ZO-one .by treatment with an aqueous sodium hydroxide solution. This product was identical with the 3,8,11a,17 trihydroxypregnane-ZO-one obtained as described in Preparation 23.

In the same manner as given above Preparation 19 through Preparation 24, other 11aacyloxy-3a (or B), .1-7 dihydroxy'pregnane120- ones are prepared, including 3,8,17-dihydroxyllla-propionoxy .pregnane-20-one; 3,3,1'7-dihydroxy-lla-octanolyoxypregnane 20 one; 11.- butyryloxy 73,l7 dihydroxypregnane-20 one; 3.a,17 .dihydroXy-lla valeryloxypregnane ZO- one; 311,17 dihydroxy-l'la hexanoyloxy-pregnane-20-one; 3:1,17 dihydroxy-lla-hQDtanqyl- .oxypregnane-20-one; 3a,1'7 CllhYdlQXy-lla-QC- tanoyloxypregnane-ZO-one; and the like, depending on the startingmaterial employed.

Example 1 .-3a,11a-diacetoa:y-1 Phi/drewpregnane-ZO-one The viscous oil from Preparation 19 (consisting of a mixture of 1la-acetoxy-3a,l7-dihydroxypregnane-20-one and 3a,11a,17-trihydroxypregnane-20-one, resulting from the evaporation of the extraction solvent before chromatographic purification, and which was prepared from "900 milligrams of 17(20) -oxido-3a,11a,20triacetoxypregnane, as more fully described in Preparat-ion 19), was dissolved in a mixture of erg-ht milliliters of acetic anhydride and eight milliliters of pyridine, and the resulting solution was allowed to stand for sixteen hours at room temperature. The solution wasthen poured into 150 milliliters of water, and the resulting mixture allowed to stand for two hours at room temperature to permit decomposition of the excess acetic anhydride. The solid which had precipitated was filtered, washed with water, and dried under vacuum. The crude 3a,l-1a-diacetoxy-l7-hydroxypregnane-20-one obtained, 875 milligrams,

was'identical with that :obtained .Example 12. Example 2.'3,11a-diacetoxy-1 7 -hydroxy- .pIeQnaneQZO-one Six hundred milligrams of I3a,11d,'1'7 trihydroxypregnane-ZO-one (from Preparation 519, '20, 21.01 22) was :dissolved in a mixture iofifive mil"- -liliters .of acetic anhydride and five milliliters of pyridine, and the resulting .solution allowed to standzat m temperature for zsixteen hours. The solution was then poured into 100 milliliters of water and the resulting mixture allowed to stand for one hour at room temperature to per-- mit decomposition of the excess acetic anhyhad precipitated was filwashed with water, and dried under "vacuum. "The crude product weighed '59.5'-mil'ligrams and melted at -190 degrees centigrade. Two recrystallizations using 'a mixture of ethyl 'acetate and Skelly Solve B gave 385 :milligra-ms of 3a,11a-dia.cetoxy-*l7 -l1ydr0Xypregnane-20-one as I colorless needles having a melting point of 194-195 degrees :centigrade and a specific rotation [M of minus ten degrees in chloroform.

Analysis.Per cent calculated for C25H38O62 C, 69:09; H, 8.81. Found: C, 69.25; .H, 28:85; 0, 69:26; 8.8.

Example 3..3a,11adi(l06t0$1ll 1-7 hydrorypramme-20-ona Using the procedure of -Example '2, 11"0 Imilligrams of 11a-acetoxy 3a,I7-dihydroxypregnane- ZO-one from Preparation 19 was converted to 30;,110. diacetoxy l7 hydroxypregnane=20=one using one milliliter of acetic anhydride and .one milliliter of pyridine. The product was identical with the 3a ,11a-diacetoxy-17-hydroxypregnanee 20-one obtained in Example '2.

Example 4.-3-aeeto:cy 17 hydrox'yel la-pro p'ionOxypregnane-W one Using the procedure of Example3, '3a,l7-.dih-ydroxy- 11a propionoxypregnane .200ne from Preparation 22 was converted to Ba-acetQXy-M- hydroxy- 11a. propionoxypregnane-ZG-one using acetic a-nhydride and pyridine.

Eramip'le 5.-3a,11a-dipropionory '17 h drumpregnane-ZO-one Era-ample 6.-3a,11-a dipropionozry 1 7-h1I/dr0mypregnane-ZO-one Using the procedur of Example 2, 8.a,1.1a,17-' trihydroxypregnanee20-.one (from Preparation 19, 20, 21, or 22) was treatedwith propionic anhydride in pyridine. The 3a,.ll-a-dipropionoxyl7-hydroxypregnane-20-one isolated. was identi; cal with that obtained in Example 5.

Example -7.3a,11u diprcpionowy-17-hydrorypregnane-ZO-cne Example 8.-3,11a dtacetomy 1? hydroxypregnane-ZO-one Using the procedure of Example 1, the oily product from Preparation 23, consisting of a mixture of 1la-acetoxy-3c,17-dihydroxypregnane-20- one and 3B,11a,l7 -trihydroxypregnane-20-one, was converted to 313,1la-dlfihflEtOXY-l'T-IIYGIOXY- pregnane-20-one using acetic anhydride and pyridine. Theproduct was the same as that obtained in Example 9.

Example 9.-sc,11 diacetoxy 1? hydrodypregnane-ZO-one Using the procedure of Example 2, 3;3,lla,17- trihydroxypregnane-20-one (from Preparation 23 or 24) was treated with acetic anhydride. The 35,110. diacetoxy 17 hydroxypregnane-20-one isolated gave the following analysis.

Analysis.-Per cent calculated for CZSHSSOGI C. 69.09; H, 8.81. Found: C, 69.14; H, 8.90.

Example 10.-3;3,11a diacetoxy 17 hydroflpregncme-ZO-one Using the procedure of Example 9, lla-acetoxy-3B,1"I dihydroxypregnane 20 one from Preparation 23 was treated with acetic anhydride in pyridine. The 35,1la-diacetoxy-fl-hydroxypregnane-ZO-one isolated was identical with that obtained in Example 9.

In the same manner as given above, other 311 (or B),lla-diacetoxy-l'l-hydroxypregnane 20 ones are prepared, including lla-acetoxy-l'l-hydroxy 3B propionoxypregnane 20 one; 1111. acetoxy 1'7 hydroxy 3,8 octanoyloxypregnane 20 one; 36 acetoxy 1'1 hydroxy- 11a propionoxypregnane 20 one; 318,11 dipropionoxy 17 hydroxypregnane 20 one; 35 acetoxy 17 hydroxy 11o. octanoyloxypregnane 20 one; 35,1111 dioctanoyloxy 1'7 hydroxypregnane 20 one; 3a.,11a dibutyryloxy 1'7 hydroxypregnane 20 one; 3a.,1la divaleryloxy 17 hyroxypregnane 20 one; 311,11). dihexanoyloxy 1'7 hydroxypregnane 20 one; 3a,11a diheptanoyloxy 1'7 hydroxypregnane 2O one; 3:1,11a dioctanoyloxy 1'7 hydroxypregnane 2O one; and the like.

It is to be understood that the invention is not to be limited to the exact details of operation or exact compounds shown and described, as obvious modifications and equivalents will be apparent to one skilled in the art, and the invention is therefore to be limited only by the scope of the appended claims.

We claim:

1. A 3,111 diacyloxy 1'7 hydroxypregnane 20-one, wherein the acyloxy groups have the formula AcO, Ac being the acyl radical of a hydrocarbon carboxylic acid containing from one to eight carbon atoms, inclusive.

2. A 3,111; diacyloxy 17 hydroxypregnane 20-one, wherein the acyloxy groups have the formula AcO, Ac being the acyl radical of a hydrocarbon carboxylic acid containing from one to eight carbon atoms, inclusive, and wherein the acyloxy groups are the same.

3. A 3,1111. diacyloxy 17 hydroxypregnane 20-one, wherein the acyloxy groups have the formula AcO, Ac being the acyl radical of a hydrocarbon carboxylic acid containing from one to eight carbon atoms, inclusive, and wherein the acyloxy groups are difierent.

4. A 3a,11a diacyloxy 1'7 hydroxypregnane 20-one, wherein the acyloxy groups have the formula AcO, Ac being the acyl radical of a hydrocarbon carboxylic' acid containing from one to eight carbon atoms, inclusive.

5. A 3B,11a-diacyloxy 1'7 hydroxypregnane 20-one, wherein the acyloxy groups have the formula AcO, Ac being the acyl radical of a hydrocarbon carboxylic acid containing from one to eight carbon atoms, inclusive.

6. 3a,11u. diacetoxy 17 hydroxypregnane 20-one.

7. 3aacetoxy 1'7 oxypregnane-2O one.

8. 30.,110. dipropionoxy 17 nane-20-one.

9. 35,111: diacetoxy 17 hydroxypregnane- 20-one.

10. A process for the production of a 3,11adiacetoxy-17-hydroxypregnane-20-one, which includes: mixing (1) a starting material selected from the group consisting of 3,l1,17-trihydroxypregnane-ZO-ones, 11a-acyloxy-3,17-dihydroxypregnane-ZO-ones, and mixtures of an Ila-acyloxy 3,17 dihydroxypregnane 20 one with a 3,111,17-trihydroxypregnane-20-one, and wherein an acyloxy group has the formula AcO, Ac being the acyl radical of a hydrocarbon carboxylic acid containing from one to eight carbon atoms, inclusive, and (2) an acylating agent containing an acyl radical of a hydrocarbon carboxylic acid having from one to eight carbon atoms, inclusive, to produce the desired 3,1la-diacyloxy-l7- hydroxypregnane-20-one.

11. A process for the production of a 3,1la-dlacyloxy-17-hydroxypregnane-20-one, which includes: mixing (1) an 11c-acyloxy-3,1'7-dihydroxypregnane-ZO-one, wherein the acyloxy group has the formula AcO, Ac being the acyl radical of a hydrocarbon carboxylic acid containing from one to eight carbon atoms, inclusive, and (2) an acylating agent containing an acyl radical of a hydrocarbon carboxylic acid having from one to eight carbon atoms, inclusive, and (3) separating the 3,1la-diacyloxy-1'7-hydroxypregnane-ZO-one from the reaction product.

12. A process for the production of a 3,11a-dlacyloxy-17-hydroxypregnane-20-one, which includes: mixing (1) a 3,11a,17-trihydroxypreg nane-20-one and (2) an acylating agent contain ing an acyl radical of a hydrocarbon carboxylic acid having from one to eight carbon atoms, inclusive, and (3) separating the 3,11a-diacyloxy- 17-hydroxypregnane-20-one from the reaction product.

13. A process for the production of a 3,11a-dl acyloxy-17-hydroxypregnane-20-one, which inclucies: mixing (1) a mixture consisting of an 11a acyloxy 3,17 dihydroxypregnane 20- one wherein the acyloxy group has the formula AcO, Ac being the acyl radical of a hydrocarbon carboxylic acid containing from one to eight carbon atoms, inclusive, and a corresponding 3,11a-17-trihydroxypregnane-20-one, and (2) an acylating agent containing an acyl radical of a hydrocarbon carboxylic acid having from one to eight carbon atoms, inclusive, and (3) separating the 3,1lc-diacyloxy-17-hydroxypregnane-20-one from the reaction product.

14. A process for the production of 3a,lla-dlacetoxy-l'?-hydroxypregnane-20-one which includes: mixing (1) 311,11a,1'7-trihydroxypregnane- 20-one, and (2) acetic anhydride, and (3) separating the 3a,1la-diacetoxy-l'l-hydroxypregnane- 20-one from the reaction product.

15. A process for the production of 3a,11a.-di acetoxy-l'l-hydroxypregnane-ZO-one which includes: mixing (1) 11e-acet0xy-3u,17-dihydroxyhydroxy 11a propionhydroxypreg- 17 pregnane-zo-one, and (2) acetic anhydride, and (3) separating the 3a,11a-diacetoXy-17-hydr0xypregnane-20-one from the reaction product.

16. A process for the production of 3/3,l1a-diacetoxy-17-hydroxypregnane-20-one which includes:' mixing 1) 3,6,11a,17-trihydroxypregnane-20-one, and (2) acetic anhydride, and (3) separating the 35,1111 diacetoxy 17 hydroxypregnane-20-one from the reaction product.

17. A process for the production of 3,8,11a-diacetoxy-17-hydroxypregnane-20-one which includes: mixing (1) 11a-acetoxy-3 3,17-dihydroxypregnazie-ZO-one, and (2) acetic anhydride, and

(3) separating the 3p,11a-diacetoxy-1'7-hydroxypregnane-20-one from the reaction product.

18. A process for the production of 3a-acet0xy- 17 hydroxy 11a propionoxypregnane 20- one which includes: mixing 1) 3a,17-dihydroxy- 11a-propionoxypregnane-20-one, and (2) acetic anhydride and (3) separating the 3a-acetoxy- 17 hydroxy 11a propionoxypregnane 20- one from the reaction product.

FRANK H. LINCOLN, JR.

GEORGE B. SPERO.

No references cited. 

1. A 3,11A - DIACYLOXY - 17 - HYDROXYPREGNANE20-ONE , WHEREIN THE ACYLOXY GROUPS HAVE THE FORMULA ACO, AC BEING THE ACYL RADICAL OF A HYDROCARBON CARBOXYLIC ACID CONTAINING FROM ONE TO EIGHT CARBON ATOMS, INCLUSIVE. 